Bensimon Gilbert, Doble Adam
Hôpital de la Pitié-Salpêtrière, Department of Clinical Pharmacology, Assistance Publique Hôpitaux de Paris et Université Paris VI, Paris, France.
Expert Opin Drug Saf. 2004 Nov;3(6):525-34. doi: 10.1517/14740338.3.6.525.
Riluzole is the only disease-modifying drug approved for the treatment of amyotrophic lateral sclerosis (ALS), in which it has been demonstrated to extend survival. The overall tolerability of riluzole is good and the drug can be used in all patients with ALS except those with elevated transaminase levels or active liver disease. The most frequently encountered adverse events (AEs) that appear to be attributed to riluzole are asthenia and nausea, observed in 18 and 15% of patients taking riluzole in the randomised clinical trial programme, respectively. These same AEs, albeit at a lower frequency, are also reported in Phase IV observational studies and in pharmacovigilance surveys. No unexpected AE clearly related to riluzole has emerged in the seven years that riluzole has been in extensive use in ALS patients. The most important potential safety issue with riluzole is hepatic impact with elevations of transaminases. Serum alanine aminotransferase levels more than three times the upper limit of normal are observed in 10 - 15% of patients. For this reason, strict monitoring of liver enzymes is recommended in patients with ALS taking riluzole, and treatment is contraindicated in subjects with elevated transaminases before the start of treatment. There is a suspicion that riluzole may, in rare cases, cause neutropenia, and physicians should be vigilant towards this risk.
利鲁唑是唯一被批准用于治疗肌萎缩侧索硬化症（ALS）的疾病修饰药物，已证实它可延长患者生存期。利鲁唑的总体耐受性良好，除转氨酶水平升高或患有活动性肝病的患者外，该药可用于所有ALS患者。在随机临床试验项目中，服用利鲁唑的患者中分别有18%和15%出现了似乎可归因于利鲁唑的最常见不良事件（AE），即乏力和恶心。在IV期观察性研究和药物警戒调查中也报告了同样的不良事件，不过出现频率较低。在利鲁唑广泛用于ALS患者的七年中，未出现明显与利鲁唑相关的意外不良事件。利鲁唑最重要的潜在安全问题是对肝脏的影响，表现为转氨酶升高。10% - 15%的患者血清丙氨酸转氨酶水平超过正常上限的三倍。因此，建议服用利鲁唑的ALS患者严格监测肝酶，在治疗开始前，转氨酶升高的患者禁用该药。有人怀疑利鲁唑在极少数情况下可能导致中性粒细胞减少，医生应对此风险保持警惕。
